Is the risk of venous thromboembolism in carriers of a prothrombin mutation influenced by high levels of microparticles?

Venous thromboembolism (VTE) is a complex disorder where several risk factors, including environmental, lifestyle, and genetic factors, play a part. Prothrombin gene mutation (PTM) is one of the most common genetic polymorphisms known to predispose carriers to VTE. PTM is found in 5% to 10% of patients with VTE. PTM results in an increased level of prothrombin in the blood and prothrombin plays a key role in the clotting cascade.

Microparticles are small vesicles that bud off from membranes of several cell types, for example platelets and endothelial cells in the veins, and can be found in several body fluids like blood, urine and breast milk. These particles are always present in healthy individuals, but are seen in higher amounts in patients. Therefore, they are under investigation as possible biological markers for diseases like cancer and VTE.

When the microparticles are formed there is a change in the phospholipid composition in their membranes making them more prone to induce coagulation activation. Tissue factor is a membrane protein found on some MPs that also is able to initiate the coagulation cascade.

A recent Italian study took a closer look at these highly procoagulant particles in carriers of the PTM. They aimed to study the concentration and cellular origin of MPs in PTM carriers with and without a history of VTE, and compare it to healthy controls. In addition, they also measured the clotting time of blood, and compared the clotting time of PTM carriers and controls.

The study revealed an increase in the total count of MPs in PTM carriers compared to the control group. The levels of MPs derived from platelets and endothelial cells were significantly elevated compared to the controls. The PTM carriers also had higher levels of MPs expressing tissue factor on the surface, all pointing towards increasing procoagulant properties of the blood. The clotting time was also significantly shorter in the PTM carriers, indicating that a clot would form more rapidly than in the control group.

There were 56% of the PTM carriers with a previous history of VTE. When dividing the PTM carrier group into those with and without a previous history of VTE, patients with VTE had higher plasma concentrations of MPs than those without a VTE event.

The authors of the study concluded that there is an increased level of MPs in PTM carriers and that the increased level is more pronounced in PTH carriers with a previous history of VTE.